What is the treatment approach for a patient with a Candida non-albicans infection?

Treatment of Candida Non-Albicans Infections

For invasive non-albicans Candida infections, initiate treatment with an echinocandin (caspofungin, micafungin, or anidulafungin) as first-line therapy, as these agents provide superior coverage against species with reduced azole susceptibility, particularly C. glabrata and C. krusei. 1

Initial Antifungal Selection Algorithm

For Candidemia and Invasive Infections

Echinocandins are the preferred first-line agents for non-albicans Candida species:

• Caspofungin: 70 mg loading dose, then 50 mg daily 1
• Micafungin: 100 mg daily 1, 2
• Anidulafungin: 200 mg loading dose, then 100 mg daily 1

The rationale for echinocandin preference stems from the variable and often reduced azole susceptibility patterns seen across non-albicans species, particularly C. glabrata (50% efficacy with fluconazole) and intrinsic resistance in C. krusei 3. The 2016 IDSA guidelines explicitly recommend echinocandins for suspected azole-resistant infections 1.

Species-Specific Considerations

C. glabrata:

• Echinocandins remain first-line 1
• Fluconazole shows only 50% efficacy and should be avoided as initial therapy 3
• Higher fluconazole doses (800 mg daily) may be considered only after susceptibility confirmation 1

C. krusei:

• Intrinsically resistant to fluconazole—never use fluconazole 3
• Echinocandins are preferred 1
• Voriconazole 400 mg twice daily for 2 doses, then 200 mg twice daily is recommended as step-down oral therapy for selected cases 1

C. parapsilosis:

• May have reduced echinocandin susceptibility in vitro, but clinical efficacy remains acceptable 2
• Fluconazole 400-800 mg daily is effective (81% efficacy) and can be used if susceptibility is confirmed 3, 4

C. tropicalis:

• Fluconazole shows 82% efficacy 3
• Echinocandins remain appropriate first-line agents 1

C. lusitaniae:

• Fluconazole 6-12 mg/kg daily is preferred due to known amphotericin B resistance patterns 5
• Amphotericin B should be avoided as C. lusitaniae rapidly develops resistance 5
• Echinocandins are effective alternatives 5

Transition to Azole Therapy

Step-down from echinocandin to fluconazole is recommended after 5-7 days if:

• Patient is clinically stable 1
• Isolate is susceptible to fluconazole 1
• Repeat blood cultures on antifungal therapy are negative 1
• Fluconazole dose: 400-800 mg daily (6 mg/kg) 1

This de-escalation strategy balances cost-effectiveness with maintaining therapeutic efficacy, but should never be attempted for C. krusei or fluconazole-resistant C. glabrata 1, 3.

Alternative Agents for Resistant Infections

For suspected multidrug-resistant Candida:

• Lipid formulation amphotericin B 3-5 mg/kg daily 1
• Amphotericin B deoxycholate 0.5-1.0 mg/kg daily (if lipid formulations unavailable) 1

Important caveat: Avoid amphotericin B for C. lusitaniae due to rapid resistance emergence 5.

Duration of Therapy

Continue treatment for 2 weeks after documented clearance of Candida from the bloodstream AND complete resolution of symptoms attributable to candidemia 1. This applies to candidemia without metastatic complications 1.

For deep-seated or disseminated infections, extend therapy until all clinical, laboratory, and radiographic abnormalities resolve 5.

Essential Adjunctive Measures

Central venous catheter removal is strongly recommended for all nonneutropenic patients with candidemia 1. Catheter retention is associated with treatment failure and increased mortality 1.

Daily or every-other-day blood cultures should be obtained to establish the time point of bloodstream clearance 1. This is critical for determining treatment duration.

Dilated ophthalmological examination within the first week after diagnosis to exclude endophthalmitis 1.

Site-Specific Non-Albicans Infections

Urinary Tract Infections

For candiduria due to non-albicans species:

• Oral flucytosine 25 mg/kg four times daily may be valuable, especially for non-albicans species 1
• Critical caveat: Resistance to flucytosine emerges rapidly when used as monotherapy—avoid single-agent use 1
• Fluconazole 200 mg daily for 7-14 days (if susceptible species) 1

Vulvovaginal Candidiasis

For non-albicans vulvovaginal infections:

• Azole therapy is unreliable for non-albicans species 1
• Boric acid 600 mg intravaginally daily for 14 days is highly effective: 78% cure rate for C. glabrata, 100% for C. tropicalis and C. lusitaniae 1, 4
• Topical flucytosine is an alternative 1
• Fluconazole shows variable efficacy: 60% for C. glabrata, 81% for C. parapsilosis 4

The 2024 expert review emphasizes the urgent need for new agents targeting azole-resistant vaginal non-albicans species, as current options remain limited 6.

Special Populations

Neutropenic Patients

Initial therapy options:

• Lipid formulation amphotericin B 3-5 mg/kg daily 1
• Echinocandin (caspofungin, micafungin, or anidulafungin) 1
• Transition to oral fluconazole 400 mg daily after clinical stabilization and susceptibility confirmation 1

Neonates

For disseminated non-albicans infections:

• Fluconazole 12 mg/kg daily if susceptible species (e.g., C. lusitaniae) 5
• Amphotericin B deoxycholate 1 mg/kg daily for amphotericin-susceptible species 1
• Avoid amphotericin B for C. lusitaniae 5

Critical Pitfalls to Avoid

Never use fluconazole empirically for non-albicans Candida without species identification and susceptibility testing, as resistance patterns vary dramatically between species 6, 3. C. krusei is intrinsically resistant, and C. glabrata shows only 50% response rates 3.

Do not assume amphotericin B is universally effective—C. lusitaniae rapidly develops resistance during therapy 5.

Avoid premature discontinuation of therapy before completing 2 weeks after bloodstream clearance, as this leads to relapse 1.

Do not use flucytosine monotherapy due to rapid resistance emergence 1.

In critically ill patients with septic shock and risk factors for invasive candidiasis, delayed initiation of antifungal therapy increases mortality—start empiric echinocandin therapy immediately while awaiting culture results 1.